Antiallergic agents

ABSTRACT

An antiallergic agent which is characterized in containing at least one compound selected from a group consisting of 4,5-dihydroxy-2-cyclopenten-1-one represented by the following formula [I] and an optically active substance and a salt thereof as an effective component.

This application is a 371 of PCT/JP98/01150, filed Mar. 18, 1998.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to drug, food and beverage which areuseful for therapy of allergic diseases.

Prior Art

In allergic diseases represented by asthma and atopic dermatitis,release of chemical mediators from mast cells plays a big role in theallergic reaction. This reaction is induced by binding theimmunoglobulin E (IgE) to receptors on cell membranes followed bycross-linking and it is expected that an inhibitor of the IgE productionplays an effect for therapy and prevention of allergic diseases.

The reaction of the delayed type hypersensitivity is an inflammatoryreaction depending upon cellular immune induced by T lymphocytesactivated by antigen which is not removed by macrophage. Inflammatorycells are induced and activated by cytokine which is produced fromactivated T lymphocytes and release various inflammatory mediators toinduce tissue disturbances. Allergic dermatitis by a reaction of thedelayed type hypersensitivity occupies a high percentage of contact-typedermatitis and, in addition, it is a cause of onset of allergy wherebacteria, virus or drugs are antigens. Thus, it is expected that aninhibitor of the delayed type hypersensitivity plays an effect fortherapy and prevention of those allergic diseases.

Problems to be Solved by the Invention

An object of the present invention is to develop a compound which iseffective for controlling the IgE production and for inhibiting thereaction of the delayed type hypersensitivity and to offer a drug whichis useful for the therapy of allergic diseases containing said compoundas an effective component, a method for the inhibition of allergy usingsaid compound as an effective component and food and beverage containingsaid compound.

Means to Solve the Problem

In order to achieve the above-mentioned object, the present inventorshave conducted an intensive investigation and found that4,5-dihydroxy-2-cyclopenten-1-one which is a compound represented by theformula [I] (hereinafter, just referred to as “the cyclopentenone”) hasan inhibition activity of IgE production and an inhibition activity ofdelayed type hypersensitivity, and said compound is useful as aneffective component of an antiallergic agent whereupon the presentinvention has been accomplished.

Outline of the present invention is that the first feature of thepresent invention relates to an antiallergic agent which ischaracterized in containing at least one compound selected from a groupconsisting of 4,5-dihydroxy-2-cyclopenten-1-one represented by thefollowing formula [I] and an optically active substance and a saltthereof as an effective component.

The second feature of the present invention relates to a method forinhibiting allergies which is characterized in using at least onecompound selected from a group consisting of4,5-dihydroxy-2-cyclopenten-1-one represented by the above-mentionedformula [I] and an optically active substance and a salt thereof as aneffective component.

The third feature of the present invention relates to an antiallergicfood or beverage which is characterized in containing at least onecompound selected from a group consisting of4,5-dihydroxy-2-cyclopenten-1-one represented by the above-mentionedformula [I] and an optically active substance and a salt thereof as aneffective component.

BRIEF EXPLANATION OF THE DRAWINGS

FIG. 1 shows the an inhibition activity of the cyclopentenone toreaction of the delayed type hypersensitivity.

FIG. 2 shows a CD of p-dimethylaminobenzoyl derivative of(−)-cyclopentenone and a stereostructure of (−)-cyclopentenone.

FIG. 3 shows a CD of p-dimethylaminobenzoyl derivative of(+)-cyclopentenone and a stereostructure of (+)-cyclopentenone.

EMBODIMENTS OF THE INVENTION

The present invention will now be specifically illustrated ashereinafter.

The cyclopentenone represented by the formula [I] used in the presentinvention covers both isomers where the configurations of hydroxylgroups at 4- and 5-positions are cis- and trans. In the presentinvention, any of cis-cyclopentenone, trans-cyclopentenone and a mixtureof cis- and trans-cyclopentenone may be used. It is also possible to useoptically active substances thereof.

cis-Cyclopentenone may be prepared by a chemical synthesis [HelveticaChimica Acta, volume 55, pages 2838-2844 (1972)]. trans-Cyclopentenonemay be prepared either by a chemical synthesis [Carbohydrate Res.,volume 247, pages 217-222 (1993)] or by heating uronic acid such asglucuronic acid, uronic acid derivative such as glucuronolactone or asubstance containing the same (refer to PCT/JP97/03052). In the presentinvention, it is also possible to use such a heated product or partiallypurified product or purified product thereof.

For example, when D-glucuronic acid is used as a uronic acid and its 1%solution is heated at 121° C. for four hours, the cyclopentenone isproduced in the heat-treated substance. The cyclopentenone in thisheat-treated substance is extracted with a solvent and the extract isconcentrated. Then, this concentrated extract is separated by means of asilica gel column chromatography, the eluted cyclopentenone fraction isconcentrated, the cyclopentenone is extracted with chloroform from theconcentrate and the extract of the concentrate is subjected to a normalphase column chromatography whereupon the cyclopentenone in theheat-treated substance is isolated.

Physical property of the cyclopentenone will be given as hereunder.Incidentally, a mass spectrometric analysis of the cyclopentenone wasconducted using a mass spectrometer DX302 (manufactured by NipponDenshi). Further, measurement of an NMR using heavy chloroform as asolvent was conducted by JNM-A 500 (manufactured by Nippon Denshi).Specific rotation was measured by a DIP-370 polarimeter (manufactured byNippon Bunko); ultraviolet absorption spectrum was measured by a UV-2500spectrophotometer (manufactured by Shimadzu); and infrared absorptionspectrum (IR) was measured by an FTIR-8000 infrared spectrophotometer(manufactured by Shimadzu).

MS m/z 115 [M+H]⁺;

¹H-NMR (CDCl₃): δ 4.20 (1H, d, J=2.4 Hz, 5-H), 4.83 (1H,m, 4-H), 6.30(1H, dd, J=1.2, 6.1 Hz, 2-H), 7.48 (1H, dd, J=2.1, 6.1 Hz, 3-H).

Incidentally, the chemical shift value of the ¹H-NMR was given on abasis that the chemical shift value of CHCl₃ was 7.26 ppm.

Optical rotation: [α]_(D) ²⁰ 0° (c 1.3, water);

UV: λ_(max) 215 nm (water);

IR (KBr method): absorptions were noted at 3400, 1715, 1630, 1115, 1060,1025 cm⁻¹.

When the isolated cyclopentenone is subjected to an optical resolution,(−)-4,5-dihydroxy-2-cyclopenten-1-one and(+)-4,5-dihydroxy-2-cyclopenten-1-one are obtained. It goes withoutsaying that the cyclopentenone obtained by a synthetic method can besubjected to an optical resolution as well.

For example, the cyclopentenone is dissolved in ethanol. To thisethanolic solution is further added hexane/ethanol (94/6) to prepare acyclopentenone solution. The cyclopentenone can be optically resolvedwhen this sample solution is subjected to an HPLC using, for example, aChiral Pack AS (manufactured by Daicel Chemical Industries) under such acondition that the column temperature was 40° C. and the mobile phasewas hexane/ethanol (94/6).

Optical rotation of the optically resolved(−)-trans-4,5-dihydroxy-2-cyclopenten-1-one [hereinafter, referred to as(−)-cyclopentenone] is [α]_(D) ²⁰−105° (c 0.30, ethanol) while that ofthe optically resolved (+)-trans-4,5-dihydroxy-2-cyclopenten-1-one[hereinafter, referred to as (+)-cyclopentenone] is [α]_(D) ²⁰ +104° (c0.53, ethanol). Incidentally, the optical rotation was measured by theabove-mentioned polarimeter of the type DIP-370 (manufactured by NipponBunko).

After that, each of (−)-cyclopentenone and (+)-cyclopentenone wassubjected to structural analysis by means of mass analysis and nuclearmagnetic resonance (NMR), measurement of UV absorption spectrum andmeasurement of infrared absorption spectrum by the method mentionedalready. As a result, both optically active substances showed the sameresult as that of the cyclopentenone before the optical resolution.

Each of the optically resolved (−)-cyclopentenone and (+)-cyclopentenonewas converted to a p-dimethylaminobenzoyl derivative, the circulardichroism spectrum (CD) was measured using a circular dichroismdispersimeter of type J-720 (manufactured by Nippon Bunko) and theresult was applied to a dibenzoate chirality rule [J. Am. Chem. Soc.,volume 91, pages 3989-3991 (1969)] to determine the configuration.

CD of p-dimethylaminobenzoyl derivative of (−)-cyclopentanone andstereostructure of (−) -cyclopentenone are shown in FIG. 2. In thedrawing, the ordinate indicates molar circular dichroism while theabscissa indicates wave length (nm). Incidentally, the abovestereostructure is given hereunder as the formula [II]

CD of p-dimethylaminobenzoyl derivative of (+)-cyclopentanone andstereostructure of (+)-cyclopentenone are shown in FIG. 3. In thedrawing, the ordinate indicates molar circular dichroism while theabscissa indicates wave length (nm). Incidentally, the abovestereostructure is given hereunder as the formula [III]

As shown in FIG. 2, FIG. 3, formula [II] and formula [III], the(−)-cyclopentenone is (−)-(4R,5S)-trans-4,5-dihydroxy-2-cyclopenten-1-one while the (+)-cyclopentenoneis (+)-(4S, 5R)-trans-4,5-dihydroxy-2-cyclopenten-1-one.

The above-mentioned cyclopentenones or an optically active substancethereof may be manufactured by any method, i.e. they may be manufacturedby a method disclosed in this specification or by means of chemicalsynthesis; and trans- and cis-cyclopentenone or a mixture thereof and anoptically active substance thereof may be used in the present inventionas well.

Examples of the salt of the cyclopentenone or optically active substancethereof are pharmaceutically acceptable salts and they may be preparedby known converting methods.

The cyclopentenone reacts, for example, with an SH-containing compound(such as cysteine and glutathione) in vivo to produce a metabolicderivative which is useful as a drug. Therefore, it is believed that thepharmaceutical effect of the metabolic derivative is achieved even whenthe cyclopentenone is administered as well. The reaction product of thecyclopentenone with an SH-containing compound in vivo is presumed to beone of the metabolically effective substances.

Thus, when exemplification is done for an SR-containing compound (R-SH),it reacts with the SH-containing compound to give a compoundrepresented, for example, by the following formula [IV] or [V]. Inaddition, a compound represented by the formula [V] is converted to acompound represented by the formula [IV].

As such, the cyclopentenone is converted to each of the metabolicderivatives in the presence of an R-SH and such a metabolic derivativeproduced in vivo achieves an effect as a drug too.

(R is a residual group where an SH group is removed from theSH-containing compound.)

(R is a residual group where an SH group is removed from theSH-containing compound.)

Accordingly, the use of the cyclopentenone, its optically activesubstance or salt thereof having an object of producticn of such areaction product in vivo, i.e. a metabolic derivative, is covered by thepresent invention as well.

When at least one compound selected from the cyclopentenone, itsoptically active substance or salt thereof having an inhibition activityof IgE production and an inhibition activity of delayed typehypersensitivity is used as an effective component and is made into apharmaceutical preparation by combining with known pharmaceuticalcarriers, it is now possible to prepare anantiallergic agent. Generally,at least one of the compound selected from the cyclopentenone, itsoptically active substance or salt thereof is compounded with apharmaceutically acceptable liquid or solid carrier and, if necssary,solvent, dispersing agent, emulsifier, buffer, stabilizer, filler,binder, disintegrating agent, lubricant, etc. are added thereto to givesaid pharmaceutical preparation which may be in solid such as tablets,granules, diluted powders, powders, capsules, etc. or in liquid such assolutions, suspensions, emulsions, etc. Further, this may be in a drypreparation which can be made into liquid by adding an appropriatecarrier before use.

The pharmaceutical carrier may be selected depending upon theabove-mentioned mode of the administration and form of the preparation.In the case of oral preparations, starch, lactose, sugar, mannitol,carboxymethyl cellulose, corn starch, inorganic salts, etc. may be used.In the manufacture of oral preparations, binders, disintegrating agents,surface-active agents, lubricants, fluidity promoters,taste-correctives, coloring agents, flavors, etc. may be furthercompounded therewith.

On the other hand, in the case of parenteral preparations, they may beprepared by common methods where at least one of the compound selectedfrom the cyclopentenone, its optically active substance or salt thereofwhich is an effective component of the present invention is dissolved orsuspended in a diluent such as distilled water for injection,physiological saline solution, aqueous solution of glucose, vegetableoil for injection, sesame oil, peanut oil, soybean oil, corn oil,propylene glycol, polyethylene glycol, etc. followed, if necessary, byadding bactericides, stabilizers, isotonic agents, analgesics, etc.thereto.

The antiallergic agent of the present invention can be administered byan appropriate route depending upon the dosage form. There will be noparticular limitation for the administering route and may be conductedby oral or external means or by injection. For example, tablets, pills,granules, diluted powder, liquid, suspension, syrup and capsules may beorally administered. Injection may be administered, for example,intravenously, intramuscularly, subcutaneously or intracutaneously.Ointment, cream, etc. may be administered percutaneously. Suppositoriesmay be administered per rectum. It is also possible to prepare aqueousor non-aqueous eye drops and examples of the eye drops to beadministered to eye are ophthalmic ointment, painting liquid, sprinklingpreparation and inserting preparation. For inhalation, a solution or asuspension of the effective component in common pharmaceutical vehiclesis used and is applied, for example, as an aerosol spray for inhalation.It is also possible that dry and powdery effective component isadministered using an inhaling device or the like so that the componentcan directly contact the lung.

The dose as an antiallergic agent is not particularly specified but maybe appropriately determined depending upon the dosage form,administration method, purpose of the use and age, body weight,conditions, etc. of the patient. Usually, however, the amount of atleast one of the compound selected from the cyclopentenone, an opticallyactive substance thereof or a salt thereof contained in the preparationfor an adult is 10pg-50 mg/kg per day. As a matter of course, the dosemay vary depending upon various factors and, therefore, the dose lessthan the above-mentioned one may be sufficient in some cases while, inother cases, the dose more than the above may be necessary. The agent ofthe present invention may be administered orally as it is and, further,the agent maybe taken daily after adding to common food and/or beverageas well.

An inhibitor of the IgE production and an inhibitor of the delayed typehypersensitivity containing at least one compound selected from thecyclopentenone, an optically active substance thereof or a salt thereofas an effective component can be made into a pharmaceutical preparationby the same manner as in the case of the above-mentioned antiallergicagent and can be administered by the same manner as in the case of theantiallergic agent.

Further, the cyclopentenone, an optically active substance thereof or asalt thereof may be used as a material for the antiallergic food orbeverage. When the cyclopentenone, an optically active substance thereofor a salt thereof is taken, symptoms of the diseases caused by the IgEproduction and delayed type hypersensitivity can be significantlyimproved and, in addition, said compound has an excellent preventiveactivity to said diseases as well.

There is no particular limitation for the method of manufacturingantiallergic food or beverage but cooking, processing and commonly-usedmanufacturing methods for food or beverage may be applied provided thatat least one compound selected from the cyclopentenone, an opticallyactive substance or a salt thereof having an inhibition activity of IgEproduction and an inhibition activity of delayed type hypersensitivityis contained in the resulting food or beverage as an effectivecomponent.

There is no particular limitation for the shape of antiallergic food orbeverage so far as at least one compound selected from thecyclopentenone, an optically active substance or a salt thereof havingan antiallergic action is contained therein, added thereto and/ordiluted therein as an effective component. Thus, the shape includes theones which can be orally taken such as tablets, granules, capsules, geland sol.

A method for the inhibition of allergy offered by the use of thecyclopentenone or optically active substance or salt thereof as aneffective component is useful in a study of onset mechanism of allergyand in a screening of antiallergic agents.

Therefore, the drug, food or beverage inhibits the IgE, production andis very useful for improvement and/or therapy of the diseases which ismediated or worsened by the IgE production such as allergic diseasescaused by the IgE including bronchial asthma, allergic rhitinis, atopicdermatitis, allergic conjunctivitis, urticaria and anaphylactic shock.It also inhibits the delayed type hypersensitivity and is useful fortherapy and prevention of the diseases accompanied by a delayed typehypersensitivity such as contact sensitivity, allergic contactdermatitis, bacterial allergy, fungal allergy, viral allergy, drugallergy, thyroiditis and allergic encephalitis.

No toxicity was observed in the compound used in the present inventioneven when the dose which is effective to achieve those physiologicalactivities is administered. In the case of oral administration forexample, no dead case was observed in rats by a single oraladministration of 100 mg/kg of any of the cyclopentenone, an opticallyactive substance or a salt thereof.

EXAMPLES

The present invention will be further illustrated by way of thefollowing examples although the present invention is never limited tothose examples. Incidentally, “%” used in the examples stands for “% byweight”.

Referential Example 1

D-Glucuroic acid (G 5269; manufactured by Sigma) (10 g) was dissolved in1 liter of water, heated at 121° C. for four hours and concentrated invacuo until about 10 ml. This was mixed with 40 ml of an upper layer ofa 3:2:2 mixture of butyl acetate, acetic acid and water and centrifugedand the resulting supernatant liquid was concentrated in vacuo untilabout 10 ml.

The above extract was applied to silica gel (BW-300SP,; 2×28 cm;manufactured by Fuji Silycia) for a column chromatography and separatedusing an upper layer of a 3:2:2 mixture of butyl acetate, acetic acidand water as an eluate at the flow rate of about 5 ml/minute under apressure of 0.2 kg/cm² using a compressor. Fractionation was conductedto make a volume of one fraction 10 ml and a part of each fraction wasanalyzed by a thin layer chromatography whereupon cyclopentenone of ahigh purity was contained in 61st to 80th fractions. Those fractionswere collected, concentrated in vacuo, extracted with 40 ml ofchloroform and the extract was concentrated in vacuo to afford 100 mg ofcyclopentenone.

The fraction was separated by means of a normal phase HPLC using aPalpack type S column and, when a detection was conducted by anultraviolet absorption of 215 nm, the purity was found to be 98%.

The above cyclopentenone (113.9 mg) was dissolved in 2.85 ml of ethanol.To this ethanolic solution was added 3.85 ml of hexane/ethanol (94/6) toprepare a cyclopentenone solution (17 mg/ml). This solution was filteredthrough a filter of 0.5 μm to prepare a sample solution for an opticalresolution HPLC.

This sample solution was applied to an optical resolution HPLC, each ofthe fractions of the (−)-cyclopentenone in the earlier peak and the(+)-cyclopentenone in the later peak was collected and evaporated todryness in vacuo to give 43.2 mg of the (−)-cyclopentenone and 43.0 mgof the (+)-cyclopentenone.

Conditions for Optical Resolution HPLC.

Columns: Chiral Pack AS (manufactured by Daicel) 2.0 cm×25.0 cm

Column temperature: 40° C.

Mobile phase: hexane/ethanol (94/6)

Flow rate: 14.0 ml/minute

Detection: UV 210 nm

Amount of the charged sample: 150 μl (2.55 mg).

Each of the (−)-cyclopentenone and (+)-cyclopentenone obtained hereincontains about 1% of enantiomer and, therefore, they were subjected toan optical resolution under the above-mentioned conditions again. As aresult, 19.7 mg of the (−)-cyclopentenone containing no enantiomer wasobtained from 30.0 mg of the (−)-cyclopentenone of the earlier peakwhile, from 37.4 mg of the (+)-cyclopentenone of the later peak, 27.7 mgof the (+)-cyclopentenone containing no enantiomer was obtained.Incidentally, the eluting times in optical resolution HPLC of the(−)-cyclopentenone and (+)-cyclopentenone were 33 minutes and 40minutes, respectively.

Example 1

(1) BALB/c male mice (Nippon Clare) (five weeks age; five mice pergroup) were sensitized by intraperitoneal administration of 100 μl of0.01% physiological saline solution of egg white albumin (Sigma) and 100μl of alum (trade name: Imject Alum; Pearce) and, 11 days thereafter,peripheral blood was collected from vein of eyeground.

The collected blood was centrifuged (2,000 rpm for five minutes), plasmawas separated and the total IgE amount in the plasma was measured bymeans of ELISA (IgE Mouse EIA Kit; Seikagaku Corporation).

In the group to which the cyclopentenone was administered, 10 mg/kg wascompulsorily administered per os once daily from the date of antigensensitization until the day before the blood collection.

In the control group, distilled water was orally administered by thesame manner as above and the non-sensitized group was named as anon-treated group.

The result is given in Table 1. An increase in total IgE. amount inplasma by sensitization with egg white albumin was suppressed byadministration of the cyclopentenone.

TABLE 1 Total IgE Amount in Plasma (ng/ml) Average ± SEM Non-TreatedGroup 0 Control Group 742.6 ± 366.0 Cyclopentenone-Given Group 355.8 ±127.5

(2) Male rats of Wistar strain of five weeks age (one group consistingof five rats) (Nippon SLC) were sensitized by an intraperitonealinjection of 100 μl of 0.01% solution of egg white albumin (Sigma) in anaqueous physiological saline solution and 100 μl of Alum (trade name:Imject Alum; Pierce) and, after 14 days, blood was collected fromabdominal artery.

The collected blood was centrifuged (at 2000 rpm for five minutes),plasma was separated and the amount of antigen-specific IgE was measuredby a 48-hour rat passive cutaneous anaphylaxis (PCA) reaction.

Thus, serum was diluted with a physiological saline solution in asuccessively doubling manner ranging from ¼ to {fraction (1/64)} andeach 0.1 ml thereof was subcutaneously injected to hair-clipped back ofmale rats of Wistar strain of seven weeks age. After 48 hours from thesubcutaneous injection, 1 ml of a mixture of 0.05% egg white albumin and0.5% Evans Blue (manufactured by Nacalai Tesque) was injected from tailvein. After 30 minutes from the injection from the tail vein, rats weresubjected to decapitation and to exanguinated death, blue spots appearedon the back were observed, the spots with a diameter of 5 mm or morewere judged to be positive and the highest dilution was adopted as anIgE titer.

In the cyclopentenone-administered groups, 1 mg/kg or 10 mg/kg ofcyclopentenone was intraperitoneally administered once daily for threedays from the antigen-sensitized day while, in the control group,distilled water was intraperitoneally administered by the same manner.

TABLE 2 IgE Titer Control Group 64 Cyclopentenone-administered groups  1mg/kg/day 16 10 mg/kg/day  <4

An increase in the antigen-specific IgE amount by sensitization with eggwhite albumin was inhibited by administration of cyclopentenone in adose-dependent manner.

As such, the IgE production was inhibited by the cyclopentenone. Similarinhibition activity of IgE production was noted in (−)-cyclopentenoneand (+)-cyclopentenone.

Example 2

C57BL/6 mice (female, five weeks age, weighed about 20 g) were purchasedfrom Nippon SLC and used for the experiment: after a preliminarybreeding for one week at our end. Ovine erythrocyte (manufactured byShimizu Jikken Zairyo) which is an antigen provoking the reaction of thedelayed type hypersensitivity was washed three times with aphysiological saline solution (manufactured by Otsuka Pharmaceutical) tomake 1'10⁹ cells/ml and 200 μl of it was intraperitoneally injected tomice to subject to an antigen sensitization.

After five days from the sensitization, 40 μl of antigen which wasprepared by the same manner was injected to right paw to induce anantigen whereby pedal edema was provoked. From the antigen-sensitizeddate, cyclopentenone was intraperitoneally administered to mice (onegroup consisting of five mice) once daily at the dose of 1 mg/kg or 10mg/kg for three days.

After two days from the antigen induction, volume of right paw of themice was measured by a measuring device for pedal edema (manufactured byUgo Basile) and used as an index for DTH. The measured value was givenby calculating the increasing rate from the right paw volume of the micemeasured before the antigen induction.

The result is shown in FIG. 1. Thus, FIG. 1 shows the an inhibitionactivity of the cyclopentenone to reaction of the delayed typehypersensitivity where the ordinate indicates an increasing rate (%)while the abscissa indicates a dose of the cyclopentenone (mg/kg).Incidentally, ** in the drawing means that it is significant to thecontrol in p<0.01.

Administration of 1 mg/kg of the cyclopentenone suppressed the reactionof the delayed type hypersensitivity and administration of 10 mg/kgshowed a significant inhibition activity to reaction of the delayed typehypersensitivity.

Incidentally, (−)-cyclopentenone and (+)-cyclopentenone showed similareffects as well.

Example 3

Injection Preparations.

(1) Cyclopentenone was added to a physiological saline solution (aslisted in the Japanese Pharmacopoeia) in a concentration of 1% toprepare an injection preparation.

(2) (−)-Cyclopentenone and glycyrrhizic acid were added to aphysiological saline solution (the same as above) in concentrations of0.5% and 0.1%, respectively, to prepare an injection preparation.

Example 4

Tablets.

(1) A tablet containing 100 mg of cyclopentenone and an appropriateamount of microcrystalline cellulose was prepared and coated with sugarto manufacture a tablet preparation.

(2) A tablet containing 0.1 mg of (+)-cyclopentenone, 10 mg ofdipotassium glycyrrhizinate and an appropriate amount ofmicrocrystalline cellulose was prepared and coated with sugar tomanufacture a tablet preparation.

MERIT OF THE INVENTION

In accordance with the present invention, an antiallergic agentcontaining at least one compound selected from the cyclopentenone oroptically active substances thereof or salts thereof having aninhibition activity of IgE production and an inhibition activity ofdelayed type hypersensitivity as an effective component is offered.

Because of the inhibition activity of IgE production and the inhibitionactivity of delayed type hypersensitivity of the cyclopentenone oroptically active substance or salt thereof, when food or beveragecontaining such a compound is taken, the IgE production is inhibited andreaction of the delayed type hypersensitivity is inhibited whereuponsuch a food or beverage is an antiallergic food or antiallergic beveragewhich is quite useful for improvement of symptoms of the diseasesmediated by the IgE production and worsened by production of said factorsuch as bronchial asthma, allergic rhinitis, atopic dermatitis, allergicconjunctivitis, urticaria, anaphylactic shock, contact hypersensitivity,etc. and for prevention of said diseases as well. It is also useful forthe therapy and prevention of the diseases accompanied by the delayedtype hypersensitivity such as contact hypersensitivity, allergic contactdermatitis, bacterial allergy, fungal allergy, viral allergy, drugallergy, thyroiditis, allergic encephalitis, etc.

Furthermore, the method of the present invention is highly useful forthe inhibition of allergy such as controlling the amount of IgEproduction.

What is claimed is:
 1. A method for the inhibition of allergy,comprising administering to an individual in need of such inhibition atleast one compound selected from the group consisting of4,5-dihydroxy-2-cyclopenten-1-one represented by the following formula[I] (I)

an optically active substance and a salt thereof as an effectivecomponent.